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Woman walking in fiery neuron forest

Exploring the science behind VMS

The role of KNDy neurons in vasomotor symptoms (VMS) associated with menopause

During the menopausal transition, many women experience VMS, commonly referred to as hot flashes and night sweats.1

Recent scientific discoveries have shown that VMS associated with menopause:2-6

  • are not related to declining estrogen alone
  • result from dual events in the thermoregulatory centre of the hypothalamus:
    1. Unopposed neurokinin B (NKB) signalling
    2. Altered activity of kisspeptin/neurokinin B/dynorphin (KNDy) neurons
     

The resulting VMS include the uncomfortable and often disruptive feelings of overheating and sweating.1-3,7

 

VMS can be defined not only by their frequency but also by their severity.8,9

Mild

Sensation of heat without sweating

Moderate

Sensation of heat with sweating, able to continue activity

Severe

Sensation of heat with sweating, causing cessation of activity

Up to 80% of women will be affected by VMS, the most commonly reported symptoms related to menopause.10-13

Get the latest updates related to VMS

References

  1. Monteleone P, Mascagni G, Giannini A, Genazzani AR, Simoncini T. Symptoms of menopause - global prevalence, physiology and implications. Nat Rev Endocrinol. 2018;14(4):199-215.
  2. Padilla SL, Johnson CW, Barker FD, Patterson MA, Palmiter RD. A neural circuit underlying the generation of hot flushes. Cell Rep. 2018;24(2):271-7.
  3. Krajewski-Hall SJ, Blackmore EM, McMinn JR, Rance NE. Estradiol alters body temperature regulation in the female mouse. Temperature. 2018;5(1):56-69.
  4. Wakabayashi Y, Nakada T, Murata K, et al. Neurokinin B and dynorphin A in kisspeptin neurons of the arcuate nucleus participate in generation of periodic oscillation of neural activity driving pulsatile gonadotropin-releasing hormone secretion in the goat. J Neurosci. 2010;30(8):3124-32.
  5. Rapkin AJ. Vasomotor symptoms in menopause: physiologic condition and central nervous system approaches to treatment. Am J Obstet Gynecol. 2007;196(2):97-106.
  6. Modi M, Dhillo WS. Neurokinin 3 receptor antagonism: a novel treatment for menopausal hot flushes. Neuroendocrinology. 2019;109(3):242-8.
  7. Krajewski-Hall SJ, Miranda Dos Santos F, McMullen NT, Blackmore EM, Rance NE. Glutamatergic neurokinin 3 receptor neurons in the median preoptic nucleus modulate heat-defense pathways in female mice. Endocrinology. 2019;160(4):803-16.
  8. Food and Drug Administration. Guidance for Industry: Estrogen and Estrogen/Progestin Drug Products to Treat Vasomotor Symptoms and Vulvar and Vaginal Atrophy Symptoms — Recommendations for Clinical Evaluation. January 2003.
  9. Todorova L, Bonassi R, Guerrero C, et al. Prevalence and impact of vasomotor symptoms due to menopause among women in Brazil, Canada, Mexico, and Nordic Europe: a cross-sectional survey. Menopause. 2023;30(12):1179-1189. 
  10. Thurston RC. Vasomotor symptoms. In: Crandall CJ, Bachman GA, Faubion SS, et al., eds. Menopause Practice: A Clinician's Guide. 6th ed. Pepper Pike, OH: The North American Menopause Society, 2019;43-55.
  11. Avis NE, Crawford SL, Greendale G, et al. Duration of menopausal vasomotor symptoms over the menopause transition. JAMA Intern Med. 2015;175(4):531-9.
  12. Yuksel N, Evaniuk D, Huang L, et al. Guideline No. 422a: Menopause: vasomotor symptoms, prescription therapeutic agents, complementary and alternative medicine, nutrition, and lifestyle. J Obstet Gynaecol Can. 2021 Oct;43(10):1188-1204.e1.
  13. Menopause Foundation of Canada. The Silence and the Stigma: Menopause in Canada. 2022. Accessed February 7, 2024. https://menopausefoundationcanada.ca/menopause-in-canada-report/